A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 282
- 试验地点
- 216
- 主要终点
- Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Independent Review Committee (IRC)
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Adequate organ function
- •Platelets greater than or equal to (≥)75 x 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L
- •Kidney function: Estimated creatinine clearance ≥40 milliliters per minute (mL/min)
排除标准
- •Known or suspected Richter's transformation at any time preceding enrollment
- •Prior systemic therapy for CLL/SLL
- •Presence of 17p deletion
- •Central nervous system (CNS) involvement
- •Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
- •Significant cardiovascular disease
- •Active hepatitis B or hepatitis C
- •Active cytomegalovirus (CMV) infection
- •Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
- •Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
- •Concurrent use of investigational agent or anticancer therapy except hormonal therapy
- •Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
- •Vaccination with a live vaccine within 28 days prior to randomization
- •Patients with the following hypersensitivity:
- •Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or bendamustine
- •Prior significant hypersensitivity to rituximab
研究组 & 干预措施
Arm A - Pirtobrutinib
Participants received pirtobrutinib 200 milligrams (mg) orally once daily in continuous 28-day cycles until disease progression or unacceptable toxicity.
干预措施: Pirtobrutinib (Drug)
Arm B - Bendamustine Plus Rituximab
Participants received bendamustine 90 milligrams per square meter (mg/m²) intravenously on Days 1 and 2 of each 28-day cycle (Cycles 1-6) plus rituximab 375 mg/m² intravenously on Cycle 1 Day 1, then 500 mg/m² on Day 1 of Cycles 2-6. Eligible participants in Arm B crossed over to receive pirtobrutinib following independent review committee (IRC)-confirmed progressive disease (PD).
干预措施: Rituximab (Drug)
Arm B - Bendamustine Plus Rituximab
Participants received bendamustine 90 milligrams per square meter (mg/m²) intravenously on Days 1 and 2 of each 28-day cycle (Cycles 1-6) plus rituximab 375 mg/m² intravenously on Cycle 1 Day 1, then 500 mg/m² on Day 1 of Cycles 2-6. Eligible participants in Arm B crossed over to receive pirtobrutinib following independent review committee (IRC)-confirmed progressive disease (PD).
干预措施: Bendamustine (Drug)
结局指标
主要结局
Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Independent Review Committee (IRC)
时间窗: From randomization until documented disease progression or death (up to 40 months)
PFS, as assessed by IRC, is defined as the time from randomization until documented disease progression as per iwCLL (International Workshop on Chronic Lymphocytic Leukemia) 2018 criteria, or death from any cause, whichever occurs first.
To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine and rituximab (Arm B)
时间窗: Up to approximately 5 years
Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Response Criteria
次要结局
- Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Investigator(From randomization until documented disease progression or death (up to 40 months))
- To Evaluate the Effectiveness of Arm A Compared to Arm B: Overall Survival (OS)(Up to approximately 5 years)
- Arm A Compared to Arm B: Time to Next Treatment (TTNT), Assessed by Investigator(From randomization until initiation of the subsequent anticancer therapy or death (up to 41 months))
- Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by IRC(From randomization until subsequent anticancer therapy, disease progression or death (up to 40 months))
- Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by Investigator(From randomization until subsequent anticancer therapy, disease progression or death (up to 40 months))
- Arm A Compared to Arm B: Duration of Response (DOR), Assessed by IRC(From first documented response until the first documented disease progression or death (up to 35 months))
- Arm A Compared to Arm B: Duration of Response (DOR), Assessed by Investigator(From first documented response until the first documented disease progression or death (up to 35 months))
- Arm A Compared to Arm B: Time to Worsening (TTW) of CLL/SLL-related Symptoms as Measured by the EORTC QLQ-C30 and IL-58(From randomization up to 37 months)
- Arm A Compared to Arm B: Time to Worsening (TTW) of Physical Functioning as Measured by the Physical Function Domain of the EORTC-QLQ-C30(From randomization up to 37 months)
- To evaluate the effectiveness of Arm A compared to Arm B: Progression-free survival (PFS)(Up to approximately 5 years)
- To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms(Up to approximately 5 years)
- To evaluate the effectiveness of Arm A compared to Arm B: Time to next treatment (TTNT)(Up to approximately 5 years)
- To evaluate the effectiveness of Arm A compared to Arm B: Overall survival (OS)(Up to approximately 5 years)
- To evaluate the effectiveness of Arm A compared to Arm B: Overall response rate (ORR)(Up to approximately 5 years)
- To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR)(Up to approximately 5 years)
- To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning(Up to approximately 5 years)